Oncogenic roles of TOPK and MELK, and effective growth suppression by small molecular inhibitors in kidney cancer cells

// Taigo Kato 1 , Hiroyuki Inoue 1 , Seiya Imoto 2 , Yoshinori Tamada 2 , Takashi Miyamoto 3 , Yo Matsuo 3 , Yusuke Nakamura 1,4 and Jae-Hyun Park 1 1 Department of Medicine, The University of Chicago, Chicago, IL, USA 2 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan 3 OncoTherapy Science Inc., Kawasaki, Japan 4 Department of Surgery, The University of Chicago, Chicago, IL, USA Correspondence to: Yusuke Nakamura, email: // Keywords : kidney cancer, TOPK, MELK, molecular target, kinase inhibitor Received : November 25, 2015 Accepted : February 09, 2016 Published : February 26, 2016 Abstract T–lymphokine-activated killer cell–originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells. Small molecular compound inhibitors against TOPK (OTS514) and MELK (OTS167) effectively suppressed the kidney cancer cell growth, and the combination of these two compounds additively worked and showed the very strong growth suppressive effect on kidney cancer cells. Collectively, our results suggest that both TOPK and MELK are promising molecular targets for kidney cancer treatment and that dual blockade of OTS514 and OTS167 may bring additive anti-tumor effects with low risk of side effects.